THE ROLE of CYSTATHIONINE-γ-LYASE in BLUNT CHEST TRAUMA in CIGARETTE SMOKE EXPOSED MICE

Clair Hartmann, Sebastian Hafner, Angelika Scheuerle, Peter Moller, Markus Huber-Lang, Birgit Jung, Benedikt Nu'baum, Oscar McCook, Michael Groger, Florian Wagner, Sandra Weber, Bettina Stahl, Enrico Calzia, Michael Georgieff, Csaba Szabo, Rui Wang, Peter Radermacher, Katja Wagner

    Research output: Contribution to journalArticlepeer-review

    8 Scopus citations

    Abstract

    Pretraumatic cigarette smoke (CS) exposure aggravates posttraumatic acute lung injury (ALI). Cystathionineg-lyase (CSE) protects against ALI and CS exposure-induced chronic obstructive lung disease (COPD). Therefore, we tested the hypothesis whether genetic CSE knockout (CSE-/-) would aggravate posttraumatic ALI after CS exposure. After 3 to 4 weeks of CS exposure, anesthetized wild-type (WT) and CSE-/- mice underwent blunt chest trauma, surgical instrumentation and 4 h of lung-protective mechanical ventilation. We measured hemodynamics, lung mechanics, gas exchange, metabolism, and acid'base status together with blood and tissue cytokine and chemokine levels, tissue expression of mediator proteins, parameters of oxidative and nitrosative stress, and histology. CSE-/- mice without CS exposure showed higher cytokine and chemokine levels, and this was further enhanced by CS exposure, particularly in males. CS exposure in WT mice aggravated posttraumatic alveolar membrane thickening, dystelectasis, and inflammatory cell accumulation, which was associated with higher thoracopulmonary compliance. Pretraumatic CS exposure in CSE-/- mice produced a similar response, except for less alveolar membrane thickening, most likely due to lung hyperinflation. CSexposed WT mice showed the most pronounced metabolic acidosis, while CS exposure in CSE-/- mice resulted in the lowest blood glucose levels. Urinary output and anesthesia rate were highest in male CS-exposed CSE-/- animals. In conclusion, in murine acute-on-chronic pulmonary disease, CSE knockout aggravated posttraumatic inflammation, which was further worsened upon pretraumatic CS exposure, and this effect was particularly pronounced in males. Hence, maintaining CSE expression is critically important for stress adaptation during ALI and CS-induced COPD, most likely in a gender-dependent manner.

    Original languageEnglish (US)
    Pages (from-to)491-499
    Number of pages9
    JournalShock
    Volume47
    Issue number4
    DOIs
    StatePublished - Apr 1 2017

    Keywords

    • Acute lung injury
    • chemokines
    • chronic obstructive pulmonary disease
    • cystathionine-γ-lyase
    • cytokines
    • gluconeogenesis
    • hydrogen sulfide
    • nitrosative stress
    • oxidative stress
    • static compliance

    ASJC Scopus subject areas

    • Emergency Medicine
    • Critical Care and Intensive Care Medicine

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